MRD-driven strategy following IsaKRD induction in transplant-eligible NDMM: Primary endpoints of the phase 3 MIDAS trial.

Abstract

7500 Background: The phase III IFM2020-02-MIDAS study (NCT04934475) evaluated a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Results from the IsaKRD induction phase have been previously published (Perrot et al., Blood, 2025). Here, we present the results from the MRD-driven consolidation phase of the trial. Methods: MIDAS is a multicenter, open-label, randomized phase 3 trial involving transplant-eligible patients aged 18-65 with NDMM. Patients achieving post-induction MRD negativity at a threshold of 10⁻⁵ by next-generation sequencing (NGS) were randomized to either 6 additional cycles of IsaKRD (Arm A) or autologous stem cell transplantation (ASCT) followed by 2 cycles of IsaKRD (Arm B), followed by lenalidomide maintenance. MRD-positive patients after induction (MRD ≥10⁻⁵) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance. Randomization was stratified by cytogenetic risk and center for both comparisons, and by MRD negativity at 10⁻⁶ post-induction for the Arm A vs. Arm B comparison. The primary endpoint was MRD negativity at 10⁻⁶ (by NGS) prior to maintenance for both comparisons. Results: A total of 485 patients with post-induction MRD negativity were randomized to Arm A (n=243) or Arm B (n=242). The pre-maintenance MRD negativity rates at 10⁻⁶ were 84% in Arm A and 86% in Arm B (Odds Ratio [OR] 1.17, 95% confidence interval [CI] 0.64–2.76, p=0.64). Additionally, 233 MRD-positive patients (10⁻⁵) were randomized to Arm C (n=109) or Arm D (n=124), with 19 patients (15%) not receiving the planned tandem ASCT. Pre-maintenance MRD negativity rates at 10⁻⁶ were 40% in Arm C and 32% in Arm D (OR 0.73, 95% CI 0.42–1.25, p=0.31). During the consolidation phase, 5 patients experienced disease progression (2 in Arm A, 0 in Arm B, 0 in Arm C, 3 in Arm D), and 2 patients died without progression in Arm A. No new safety signals were identified compared to the induction phase. The study is ongoing. With a median follow-up of 16.8 months in Arms A/B and 16.3 months in Arms C/D, sustained MRD negativity and progression-free survival (PFS) data are not yet available. Conclusions: After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10⁻⁵, MRD negativity rates at 10⁻⁶ before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10 -5 , tandem ASCT did not significantly improve MRD negativity rates at 10⁻⁶ before maintenance. Further follow-up, including sustained MRD negativity and PFS data, is needed to evaluate the long-term outcomes of this MRD-adapted strategy. Clinical trial information: NCT04934475 .